Currently, the most common modes of treatment of primary and secondary cancer of organs consist of surgical resection, radiotherapy and/or systemic chemotherapy. The side effects of cytotoxic agents associated with systemic chemotherapy are well known. Some common toxicities are bone marrow suppression leading to neutropenia, anaemia and thrombocytopenia; hair follicle cell damage leading to alopecia; induction of apoptosis of gastrointestinal crypt cells leading to diarrhea and oral ulceration. Additionally, different drug classes can cause other toxicities including heart damage, peripheral nerve damage leading to sensory-motor neuropathy, renal damage, and pulmonary fibrosis.
For many organ cancers, the only curative treatment option is surgical resection. However, surgical resection is not always an option. Often the cancer is not detected until it is in an advanced state and has metastasized throughout the organ making it unresectable. Systemic chemotherapy in these cases has disappointing response rates with moderate increase in patient survival. Chemotherapy doses are often limited by their toxic side effects on other organs. Therefore, it is desirable to apply the chemotherapy only to the organ being treated. Treating an isolated organ can potentially enable higher doses as the drug will be concentrated in the target organ and significantly reduces or eliminates systemic toxicity. Additionally, isolated organ perfusion allows for multiple treatments in a relatively short time period as the body does not need to recover from the lasting effects of systemic toxicity.
Isolated organ perfusion has been performed using typical surgical and interventional techniques. Isolated surgical organ perfusion has been performed on the liver with encouraging results. However the trauma of surgery performed to isolate the organ prevents multiple applications of chemotherapy. Moreover, an organ cannot be completely isolated from the systemic blood flow as, even by stopping the main blood inflow and outflow; the organ will communicate with the systemic circulation via collateral connections or vessels. This is for instance the case for the liver, which besides the main vessels being the hepatic artery, the portal vein and the vena cava, is provided with collateral vessels which communicate with the systemic blood circulation. The perfused therapeutic agent will be at least partially conveyed to the patient's non-targeted organs through the systemic blood flow. This is disadvantageous for the patient as (i) it leads to a dilution of the perfused therapeutic agent dose which inhibits the effect on the targeted organ (ii) it limits the maximum dose that can be perfused to a targeted organ to the maximum dose leaked out of said organ which can be accepted by other non-targeted organs of the patient's body.
In addition, in reaction to some diseases such tumors which make organ blood flow difficult, the blood will find a way to circumvent the tumor by creating and/or connecting to other tissues and/or organs. In this case the practitioner is not aware of the newly developed connections. Said connections increase the leakage rate of the therapeutic agent or the chemotherapy drug from the perfused organ to the systemic blood flow. This result in systemic toxicity or higher blood loss during the intervention which might, in some cases, be dangerous for the treated subject and the functioning of the whole subject's body.
Up to date, the local perfusions need a large group of clinical specialist to execute a full procedure: interventional radiologist, anesthesiologist, nuclear specialist, perfusionist, oncologist, nurses. Moreover, due to the full manual control, the procedure could take more than four hours to be completed. The local perfusions have to be performed 2 to 5 times per patient. All these factors result in a treatment which is expensive. Therefore, the treatment cannot be made available due to all patients for economic reasons.
The aim of the present invention is to provide a solution to at least part of the above mentioned problems. The present invention provides a system, devices and a method for monitoring and controlling a subject's organ perfusion. The method of the invention overcomes the described problem as it provides a more patient safe and cheaper treatment.